Maintaining circulating levels of a drug or other biological factors in a subject is important for proper treatments and biological function.
Diabetes mellitus affects over 100 million individuals worldwide. In the US, the estimated healthcare costs of the 12 million affected is estimate to be 136 billion dollars annually. Diabetes mellitus is a disorder of the metabolism that is characterized by the inability of the pancreas to secrete sufficient amounts of insulin.
Insufficient amounts of insulin results in large fluctuations in blood glucose levels can have both short-term and long-term physiological consequences. Long-term complications arising from elevated blood glucose levels (hyperglycemia) in patients with Type 1 diabetes include retinopathy, neuropathy, nephropathy and other vascular complications. Low glucose levels (hypoglycemia) can lead to diabetic coma, seizures, accidents, anoxia, brain damage, decreased cognitive function, and death.
The conventional approach to glucose regulation in diabetic patients includes 3-5 daily insulin injections, with the quantity of insulin being determined by 4-8 invasive blood glucose measurements each day. This method of insulin delivery is painful, inconvenient and may be unreliable due to the pharmacokinetics of the insulin analogues that are typically used. Pen devices have been developed to make insulin delivery more convenient; however, the inability to mix insulin or insulin analogue types is a disadvantage. Several other routes of insulin delivery have been studied as an alternative to insulin injections including inhalation and transdermal insulin delivery. Others have explored the efficacy of continuous subcutaneous insulin infusion (CSII) using a pump. This has mainly been done in comparison to conventional insulin therapy or multiple daily insulin injections (MDI). Continuous subcutaneous insulin infusions by external insulin infusion pumps normally use rapid-acting insulin analogues.
Typical fixed dosage approaches assume that the metabolic demands of each day are metabolically similar, and that the fixed dosages adequately anticipate the timing and quantity of insulin that is required by the patient.
Unfortunately, blood glucose fluctuations continue to occur uncontrollably in many patients beyond the normal range of 70-120 mg/dl, exacerbating the risks of physical complications. Periodic episodes of hypoglycemia and hyperglycemia may occur when the insulin needs of the patient deviate from the levels predicted by regimen and present in the bloodstream.
The development of external insulin infusion pumps, along with the introduction of rapid acting insulin analogs has greatly aided in making intensive insulin therapy feasible. The efficacy of the insulin therapy is quantified by measurement of the percentage of glycosylated hemoglobin in the bloodstream (A1C). Values less than 6% are seen in normal healthy people without diabetes; whereas, higher percentages are indicative of sustained hyperglycemia.